Joint British Diabetes Society (JBDS) guidelines 2022 on dialysis.pptx

Management of adults
with diabetes on dialysis
August 2022

1. Yasser Matter 145 Pages

2. Recommendations For Organisation Of Care (Section 1) Recommendations For Glycaemic Assessment In People With Diabetes On Dialysis (Section 2) Recommendations For Non-Insulin Glucose Lowering Therapies (Section 3a) Recommendations For Insulin Therapy In People With Diabetes On Dialysis (Section 3b) Recommendations For Dietary Interventions For People With Diabetes On Dialysis (Section 4) Recommendations For Management Of Hypoglycaemia In People With Diabetes On Dialysis (Section 5a) Recommendations For Footcare (Section 5b) Recommendations For Retinopathy In People With Diabetes On Dialysis (Section 5c) Recommendations For Diabetic Ketoacidosis In People On Dialysis (Section 5d) Practice Points Management Of Diabetes In People Undergoing Peritoneal Dialysis – Clinical Considerations And Practice Points (Section 6) TALK OUTLINES

3. Recommendations For Organisation Of Care (Section 1) Local integrated care systems and acute trust hospitals should take into consideration that in-reach visits during dialysis unit attendance by diabetes service teams might be the most viable option to carry out regular diabetes review (annual review). To support this healthcare resources should be ringfenced and allocated accordingly. Each person undertaking in-centre mHDx should have a named link worker on the dialysis unit who can ensure that the assessments have been undertaken and have been acted upon. ( Grade 1B ) A link nurse on the haemodialysis unit will be expected to coordinate regular foot checks, blood glucose monitoring training and injection technique. This could be a healthcare assistant or a registered nurse following appropriate training and competency assessment. The link nurse would be expected to escalate foot problems for specialist foot assessment and on-going referral to the specialist foot team. (Grade 1D)

4. Recommendations For Organization Of Care (Section 1) It is recommended that a process to coordinate the management of acute metabolic, eye, cardiovascular and/or foot emergencies should be established with effective communication between the dialysis ( haemodialysis or peritoneal) unit, the specialist diabetes team and primary care. (Grade 1C) It is recommended that all people with diabetes undergoing mHDx or on a PD programme should have access to a named DSN responsible for providing support in relation to ongoing care of diabetes and its complications . Where commissioned,the DSN would be able to provide rounds on the haemodialysis unit and outpatient clinics for those on PD, offering patient education and clinical advice where necessary.

5. Recommendations For Glycaemic Assessment In People With Diabetes On Dialysis (Section 2) We suggest that HbA1c should be used with caution in people with diabetes on dialysis, as it may not provide a true reflection of prevailing glucose control, and clinicians should be aware of its deficiencies. In particular, HbA1c does not give a good reflection of GV and may not adequately identify people who are at high risk of hypoglycaemia . (Grade 2C) We suggest that HbA1c > 80 mmol /mol (9.5%) is likely to reflect poor glycaemic control, unless there is severe iron deficiency. (Grade 2C) We suggest that for people with diabetes on dialysis, direct glucose estimations ( SMBG) should routinely be offered. isCGM should also be considered for the assessment of glucose control. (Grade 2C) We recommend that all people with diabetes on dialysis treated with insulin and/or sulfonylureas must have access to SMBG. (Grade 1C)

6. Recommendations For Glycaemic Assessment In People With Diabetes On Dialysis (Section 2) Hierarchy of glycaemic goals in people with diabetes on dialysis In keeping with international consensus guidelines, the principle of time in target(TIR ) is the most useful definition of targets for this group. Therefore, we propose a hierarchy of goals as follows: 1. Avoidance of ALL severe hypoglycaemia ( requiring 3rd party assistance ) 2. Avoidance of significant hypoglycaemia (< 5mmol/L ) 3. Minimisation of time spent with glucose > 13.9mmol /L (<25% or 6h/day ) 4. Minimisation of time spent with glucose < 5mmol /L (<4% or 1h/day ) 5. Minimisation of excessive glycaemic variability ( CV>36% or SD >3.5mmol / L ) It is therefore proposed that a target range for people with diabetes on dialysis of 6–12 mmol /L and a goal of achieving >70% TIR.

7. We recommend that people with diabetes on dialysis meeting national criteria for isCGM should be offered this option and receive training and support for its optimal use. (Grade 1C) We suggest that all people with diabetes on dialysis using insulin who have recurrent hypoglycaemia or loss of hypoglycaemia awareness should be offered real-time CGM . (Grade 2C) We suggest that people with diabetes on dialysis not eligible for isCGM should be considered for regular diagnostic (6-12 monthly) CGM if their SMBG results show frequent (>5%) glucose readings below 4 mmol /L , frequent (>20%) glucose readings above 14 mmol /L , if they are unable to undertake SMBG twice a daily for 1-2 weeks periods , or if they have HbA1c < 42 mmol /mol (6.0%) or > 80 mmol /mol (9.5% ). (Grade 2C) TO conclude , HbA1c does not adequately describe glucose control in people with diabetes on dialysis. Frequent SMBG is burdensome. Therefore, use of isCGM or CGM in such patients should be considered, especially in those on therapies that may cause hypoglycaemia Recommendations For Glycaemic Assessment In People With Diabetes On Dialysis (Section 2)

8. Advantages Disadvantages SMBG Inexpensive Easily available Less HCP training Therapeutic and diagnostic success depend on frequent SMBG , High user motivation needed , Impacts QoL , Provides static measure only , Manual download for data review needed , No alarms or alerts isCGM ( Flash GM ) Less expensive than RT-CGM , Provides detailed measure of glucose assessments , Continuous assessment , Data for self-management and learning , No separate transmitter insertion , Smartphone and remote data share options , Calibration free , Recent option for alerts No predictive alarm/ alerts , Patient training needed (device use, data interpretation and adjusting treatment) , HCP training needed , Accuracy may not be reliable in low glucose settings RT-CGM Provides detailed measure of glucose assessments , Data for self management and learning , Continuous assessment , Smartphone and remote data share options , Calibration free (some versions) , Integration with automated insulin dosing systems and bolus advisors , Customisable alarm/ alerts and predictive alarm/alerts , Improved accuracy in low glucose settings compared to flash CGM Expense , Patient training needed (device use, data , interpretation and adjusting treatment) , HCP training needed

9. Example SMBG structure based on two tests per day for people with diabetes on dialysis unable to undertake diagnostic CGM. Week One Day 1 i ) Fasting (morning) ii) Before main evening meal Day 2 i ) Before dialysis ii) 30 mins after dialysis Day 3 i ) Before lunch ii) Before bed Day 4 i ) Immediately after dialysis ii) 3 hours later Day 5 i ) Fasting (morning) ii) Before bed Day 6 i ) Before dialysis ii) 4 hours after dialysis Day 7 i ) Before lunch ii) Before evening meal Week Two Repeat above for days 8-14

10. Recommendations For Non-Insulin Glucose Lowering Therapies (Section 3a) In people with declining renal function, the clearance of insulin (endogenous and exogenous) and other anti- hyperglycaemic agents declines, leading to an increased risk of hypoglycaemia . A so-called “ burnt-out diabetes” phenomenon has been described, whereby people with Type 2 diabetes ( T2D ) on dialysis may need reduced doses of medications used to treat their diabetes, with cessation of their anti-diabetic therapies transiently or permanently in a significant number of cases. Sulfonylureas , Glinides , Acarbose , Metformin and SGLT-2Is are not licensed for use in patients on dialysis. We therefore do not recommend their use in people with diabetes on dialysis. ( Grade 1B )

11. Pioglitazone is not licensed for use in patients on dialysis although it is licenced for use in patients with eGFR down to 4 mL /min and has been used safely in patients on mHDx . We therefore suggest its use with caution in people with diabetes on mHDx . (Grade 1C) The risk of hypoglycaemia is low with pioglitazone and its hepatic metabolism abolishes the need for dose adjustment when renal function declines. It has no renal elimination and is unaffected by dialysis and can be used in CKD stage 1–5 down to a clearance of 4 mL /min. Pioglitazone has been shown in a small RCT to be safe and effective for the treatment of diabetes in people on mHDx with additional positive effect on BP. Recommendations For Non-Insulin Glucose Lowering Therapies (Section 3a)

12. In addition to better glycaemic control, pioglitazone was also shown in a prospective controlled study to improve lipid profile, decrease inflammatory markers and adiponectin level and improves responsiveness to Erythropoietin ( Epo ) therapy with reduction of Epo dose in mHDx patients. Pioglitazone was shown in a recent large cohort study to be associated with significantly lower all-cause mortality and major adverse cardiovascular and cerebrovascular events than dipeptidylpeptidase-4 (DPP-4) inhibitors in people with diabetes on mHDx especially among those with dyslipidaemia and non-insulin users. Caution is particularly required in patients with , HF , Bladder cancer ,macular oedema and renal bone disease where there have been some concerns about the association between pioglitazone use and increased risk of bone fractures and macular oedema . Recommendations For Non-Insulin Glucose Lowering Therapies (Section 3a)

13. The DPP-4 inhibitors linagliptin , sitagliptin , vildagliptin and alogliptin are all licenced for use in patients on dialysis . We therefore recommend their use in people with diabetes on dialysis. Dose reductions for sitagliptin , vildagliptin and alogliptin are required. ( Grade 1B ) Given safety concerns with the use of saxagliptin in people with heart failure, we suggest saxagliptin should be avoided in individuals who have history of heart failure. Recommendations For Non-Insulin Glucose Lowering Therapies (Section 3a)

14. GLP1-receptor agonists are not licenced for use in patients with eGFR of <15 mL /min but have been used safely in patients on mHDx . We therefore suggest their use with caution in people with diabetes on mHDx . (Grade 2D) BUT no data on the use of GLP-1 receptor agonists in people with diabetes on PD so not recommended in PD . In a meta-analysis ( 2021 in the Lancet )of eight RCTs comprising more than 60,000 patients with T2D, GLP-1 RA reduced major adverse cardiovascular events (MACE) by 14%, all-cause mortality by 12%, and hospital admission for heart failure by 11% with no increase in risk of severe hypoglycaemia , retinopathy, or pancreatic adverse effects. In another meta-analysis ( 2021 in the BMJ ) , GLP-1RAs significantly reduced non-fatal stroke than SGLT-2Is Recommendations For Non-Insulin Glucose Lowering Therapies (Section 3a)

15. In people who do not have diabetes on maintenance haemodialysis ( mHDx ), blood glucose tends to fall during a mHDx session with the nadir during the third hour. mHDx may affect insulin secretion, clearance, and resistance as the result of periodic improvement in uraemia and acidosis . Glucose concentration in the dialysate of both mHDX and peritoneal dialysis (PD) patients may also influence glucose control, with lower glucose dialysates being associated with hypoglycemia. It is likely therefore, that glucose control on dialysis days may be very different to that of non-dialysis days , and that therapy may need to be adjusted accordingly. Recommendations For Insulin Therapy In People With Diabetes On Dialysis (Section 3b)

16. Recommendations For Insulin Therapy In People With Diabetes On Dialysis (Section 3b) We suggest that a reduction in insulin doses by 25 % on haemodialysis days may reduce risk of hypoglycaemia , but assessment with CGM may offer a better guide to insulin dosing on dialysis and non-dialysis days. (Grade 2C) We suggest that basal bolus regimes may be most flexible and best suited to the GV seen in people with diabetes on dialysis. (Grade 2C) We suggest that in people with diabetes on dialysis who are unable to manage a basal bolus regimen, consideration should be given to once daily regimes with longer acting insulin . (Grade 2C) TO Conclude , Pioglitazone , gliptins , GLP-1 analogues and insulin are the only recommended therapies available for use on people with diabetes on dialysis.

17. Recommendations For Dietary Interventions For People With Diabetes On Dialysis (Section 4) We recommend that individuals on mHDx / PD achieve a protein intake of >1.0 g/kg IBW & 1.0-1.2 g/kg .(Grade 1C) We recommend that individuals on mHDx achieve an energy intake of 30–40 kcal/kg ideal body weight (IBW) AND 30-35 kcal/kg for PD . (Grade 1D) To prevent unnecessary restrictions and provide health benefits , We recommend that low potassium dietary restrictions are not required unless serum potassium is persistently ≥6.0mmol/L predialysis . (Grade 1D) We recommend maintaining the inter-dialytic fluid gain (IDFG) at <4.5% of dry weight or <1.5-2 kg if the glucose control is optimized. (Grade 1D) We recommend a salt intake of <5 g/day for people with diabetes on dialysis. (Grade 1C)

18. Current guidelines indicate that nutrition support should be considered in individuals with one or more of: BMI <20 kg/m2. Unintentional non- oedema weight loss >5–10% over 3–6 months . Subjective global assessment of the nutrition status graded B/C . Intercurrent catabolic acute conditions which render normal nutrition impossible, or which prevent adequate oral intake. Accelerated loss of lean body mass with no changes to BMI and body weight have been observed in individuals with diabetes on mHDx , suggesting that anthropometric markers to estimate muscle mass should additionally be used in individuals with diabetes, such as handgrip strength . Bioimpedance or preferably multi-frequency bioelectrical impedance (MF-BIA) is recommended to assess body composition where available Recommendations For Dietary Interventions For People With Diabetes On Dialysis (Section 4)

19. Recommendations For Dietary Interventions For People With Diabetes On Dialysis (Section 4) We recommend that individuals with gastroparesis should be encouraged to have frequent small meals that are low in fat and fiber to help manage the condition. (Grade 1C) We recommend that individuals who are being considered for a kidney transplant who are overweight/obese should be encouraged to lose weight through dietary counselling on a calorie restrictive diet, making sure protein requirements are met (1.0 g/kg IBW). ( Grade 1B ) We recommend that all individuals with an elevated body mass index (BMI) who may not be considered for transplantation if unable to lose weight through diet, exercise and behavioural change should be considered for weight-reducing strategies including bariatric surgery . (Grade 1C) While GLP-1 receptor agonists have been approved for the treatment of obesity in the genera l population, the lack of experience and evidence for their use in subjects with renal failure means they cannot presently be recommended in this population, but this is an option that requires investigation. TO conclude , All people with diabetes on dialysis should have the opportunity to discuss dietary issues with a dietitian with expertise in dialysis and diabetes.

20. Recommendations For Management Of Hypoglycaemia In People With Diabetes On Dialysis (Section 5a) People on dialysis are at risk of hypoglycaemia . Blood glucose levels tend to decline during a haemodialysis session with the lowest glucose being before the third hour even though no hypoglycaemia may be reported. Mean glucose concentrations post haemodialysis are also found to be significantly lower on dialysis vs. non-dialysis day s , and 75% of hypoglycaemic events occur within 24 hours of dialysis. There is no specific guidance as to the amount of carbohydrate recommended to prevent post-dialysis hypoglycaemia . Therefore, it is recommended to ensure a hypoglycaemia treatment is always accessible to the individual, including during travelling to and from the dialysis unit. We recommend that capillary glucose should be assessed pre- and post haemodialysis . (Grade 1D) We recommend that where there is a pre-dialysis glucose of <7 mmol /L, 20–30 g low glycaemic index carbohydrat e is provided at the beginning of the haemodialysis session to prevent further decline of blood glucose level. (Grade 1D)

21. Recommendations For Management Of Hypoglycaemia In People With Diabetes On Dialysis (Section 5a) We recommend that an appropriate rapid-acting carbohydrate treatment should be provided to take into account fluid, potassium and phosphate restrictions. (Grade 1D) After treatment initiation, glucose level should be checked 15 minutes after the treatment is given. If not above 4 mmol /L, a repeat dose of the 15 g rapid glucose followed by 10–20 g low glycaemic index carbohydrate is recommended. (Grade 1C) For people who are experiencing hypoglycaemia symptoms even when the blood glucose level is above 4mmol/L . The Joint British Diabetes Societies recommends an intake of 15–20 g of carbohydrate , such as 1 medium slice of bread or 2 digestive biscuits

22. Recommendations For Footcare (Section 5b) We recommend that all people with diabetes on dialysis should be considered high risk of developing foot ulcers and are at high risk of amputation. ( Grade 1B ) We recommend that all people with diabetes on dialysis should inspect their feet daily and if they are unable to do this because of poor eyesight or frailty their carers should be advised to undertake this for them. (Grade 1C) We recommend that the heels of all people with diabetes on mHDx should be protected with a suitable pressure relieving device during haemodialysis . (Grade 1C) We recommend that all people with diabetes on dialysis should have regular podiatry review (at least 3 monthly) . (Grade 1C) We recommend that all people with diabetes on dialysis should have their feet screened monthly using a locally agreed tool and by competent staff on the dialysis unit. (Grade 1C) We recommend that if the individual has an ulcer o r there is any other concern the patient should be referred to the diabetic foot team within one working day and each dialysis unit should ensure that there is a clearly defined escalation pathway for these individuals. ( Grade 1B ) If the individual is on home dialysis , we suggest it is the responsibility of the clinician in charge of their care to ensure that they have an annual foot review and are attending review by the foot protection team. (Grade 2B) We recommend that any individual presenting with a hot swollen foot should be referred to the diabetic foot team within 24 hours . ( Grade 1B )

23. Recommendations For Retinopathy In People With Diabetes On Dialysis (Section 5c) We recommend that all people with diabetes on dialysis should be asked about when they last had retinal screening as part of their annual review. Ideally, this should have occurred within six months prior to starting dialysis in order to ensure that those who have severe non proliferative retinopathy, proliferative retinopathy or macular oedema have been referred for treatment ideally before initiating dialysis . (Grade 1C) We suggest that in those individuals identified as having severe macular or retinal disease extra care is taken to minimise intradialytic hypotension and rapid change in BP or fluid status during haemodialysis . (Grade 2D) We recommend continuing with anti-coagulation and anti-platelets therapies when indicated in patients with diabetic retinopathy on dialysis. (Grade 1C) We recommend prompt control of hypertension in patients with diabetic retinopathy on dialysis following initiation or maximisation of erythropoietin therapy. (Grade 1C) We suggest the use of ACEIs and ARBs to treat hypertension in patients with diabetic retinopathy on dialysis. (Grade 2B) We recommend that if people with diabetes on dialysis experience acute changes to their vision , they should be referred urgently to a hospital eye service for an urgent assessment and that each dialysis unit should have an escalation pathway for such individuals. ( Grade 1B )

24. Recommendations For Diabetic Ketoacidosis In People On Dialysis (Section 5d) Diabetic Ketoacidosis (DKA) is less common in people with end-stage kidney disease (ESKD) than in people with preserved renal function. An osmotic diuresis rarely occurs in oligo-anuric ESKD patients, consequently protecting them from dehydration When to Suspect DKA and test for ketones ? If T2D , CBG > 15.0 mmol/L (on 2 separate readings taken an hour apart) and symptoms suggestive of DKA . If T1D , CBG > 15.0 mmol/L and asymptomatic Symptoms suggestive of DKA : nausea/vomiting, confusion, abdominal pain, drowsiness and fruity smell on breath, deep sighing respiration ( Kussmaul breathing ). we recommend that the diagnostic criteria of DKA in ESKD are the same as for adults with preserved renal function

25. Recommendations For Diabetic Ketoacidosis In People On Dialysis (Section 5d) If blood ketones are above 3.0mmol /L, the person should have access to personnel and facilities to enable rapid and appropriate assessment and management of Diabetic Ketoacidosis (DKA). (Grade 2D) We suggest there should be a pathway in place at each haemodialysis unit for the rapid and safe prescription and administration of a bolus dose of insulin for use in an emergency. (Grade 2D) After DKA has been diagnosed, treatment should follow the JBDS DKA Guidelines update June 2022, paying particular attention to the fluid replacement regimen recommended for those on dialysis. (Grade 2D)

26. Recommendations For Diabetic Ketoacidosis In People On Dialysis (Section 5d) If there is a delay in transfer to a facility for intravenous insulin infusion, we suggest the following. (Grade 2C): a) Administration of subcutaneous bolus dose of short acting insulin at a dose of 0.05units/kg b) Hourly monitoring of CBG and blood ketones c) Clear documentation of the administered dose and timing of insulin bolus and handing this information over to the receiving team when the patient is transferred TO Conclude , All dialysis units should be able to recognise and provide initial management of hyperglycaemic emergencies in people with diabetes on dialysis. They should have rapid access to specialist diabetes care once a hyperglycaemic emergency is diagnosed.

27. Practice Points Management Of Diabetes In People Undergoing Peritoneal Dialysis – Clinical Considerations And Practice Points (Section 6) HbA1C, despite its limitations in persons with renal disease, is currently recommended as the preferred marker to assess long term glycaemic control in people with diabetes on PD. HbA1c treatment goals and targets should be individualised and other clinical parameters such as anaemia , erythropoietin treatment and PD regime must be considered when managing diabetes in people on PD. Avoid the use of GDH-PQQ based glucometers or strips as these can give rise to falsely elevated BG reading s in people undergoing PD with icodextrin . This can result in the risk of excessive insulin treatment and iatrogenic hypoglycaemia . Intermittently scanned or real time CGMs are not licensed or validated to be used in persons with PD in the UK . However, clinical experience suggests that these may be helpful to titrate insulin in order to minimise glycaemic variability and hypoglycaemia in this high-risk population. In our opinion, Flash GM or CGM may have a role in all people with diabetes on PD who are on insulin treatment. For people with diabetes on PD requiring insulin treatment we advise the use of insulin subcutaneously only , NOT intraperitoneally . Icodextrin is metabolized to maltose which cross reacts as glucose , giving falsely high glucometer values when using GDH-PQQ based glucometers. Of the glucose monitor brands currently available in the UK, Accu-Chek Go/Go S System and Accu-Chek Integra System (Roche Diagnostics ) utilize the GDH-PQQ based method hence should not be used in people undergoing PD, especially with Icodextrin . It is important to note that maltose metabolites generated during PD with Icodextrin take at least two weeks to return to baselin e, and therefore, the glucometer assay interference may persist for some time after cessation of Icodextrin usage.

28. Practice Points Management Of Diabetes In People Undergoing Peritoneal Dialysis – Clinical Considerations And Practice Points (Section 6) Exact insulin titrations and regimens should be individualized . A standard MDI or CSII (in T1D) may be preferred as it gives more flexibility towards dose titrations. A regime of long-acting analogue insulin and pre-meal rapid acting insulin is preferred . We would advise moving basal insulin to breakfast in people on CAPD and moving it to night on APD . If using glucose-based dialysates there may be a need for increased insulin doses to counter the systemic absorption of glucose from the dialysate. If there is a change from glucose based dialysate to non-glucose based dialysate such as Icodextrin , reduced insulin doses may be required to avoid subsequent hypoglycaemia . People on PD being transferred to HD , will require dose adjustments of insulin to avoid hypoglycaemia due to sudden withdrawal of the glucose containing PD regime. TO Conclude , Management of diabetes in people on peritoneal dialysis can be challenging, and specialist input may be required. Use of intermittently scanned or continuous glucose monitoring may assist management decisions.

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